HDL metabolism

The pathways of HDL metabolism and reverse cholesterol transport are complex (Fig. 3, [1]). HDL and its major apolipoprotein apoA-I are synthesized by both the intestine and the liver. A second major... 

Lipoprotein Metabolism. Figure 3 HDL metabolism and reverse cholesterol transport. 

Genetic disorders of HDL metabolism have also resulted in greater understanding of the molecular regulation of HDL metabolism. Nonsense or missense mutations in apoA-I can result in substantially reduced HDL-C levels due to rapid catabolism of structurally abnormal or truncated apoA-I proteins. Tangier disease is a rare autosomal codominant disorder characterized by markedly low HDL-C and apoA-I levels and caused... 

Rader DJ (2006) Molecular regulation of HDL metabolism and function implications for novel therapies. J Clin Invest 116 3090-3100... 

However, very low plasma levels of HDL cholesterol are also found in patients with genetically disturbed metabolic pathways that are indirectly linked to HDL metabolism. For example, many patients with lipid storage diseases like Gaucher s disease (glucocerobrosidase deficiency, OMIM 230800-231000), Nieman-Pick disease types A or (sphingomyelinase deficiency, OMIM 257200 and 607616, respectively), Niemann-Pick disease type C (OMIM 257220), hypertriglyceridemia, or diabetes mellitus present with low HDL cholesterol [22]. 

Although of much less clinical relevance, it must be emphasized that certain disturbances of HDL metabolism cause familial aggregation of elevated HDL cholesterol... 

Eckardstein Avon, FunkeH, Chirazi A, Chen-HaudenschildC, Schulte H, SchonfeldR, Kohler E, Schwarz S, Steinmetz A, Assmann G (1994) Sex-specific effects of the glutamine/histidine polymorphism in apo A-IV on HDL metabolism. Arterioscler Thromb 14 1114-1120... 

Hovingh GK, de Groot E, van der Steeg W, Boekholdt SM, Hutten BA, Kuivenhoven JA, Kastelein JJ (2005) Inherited disorders of HDL metabolism and atherosclerosis. Curr Opin Lipidol 16 139-145... 

The search for intestinal cholesterol transporters extended for many years, beginning with a debate about whether or not it was even a protein-facilitated process (4, 5). The pancreatic enzyme carboxyl ester lipase (CEL, also called cholesterol esterase) was believed to be important to this process (6,7) and several companies devoted considerable resources to the development and testing of compounds to inhibit CEL, with mixed results (8-10). These efforts were abandoned in the mid-1990s, however, after studies with gene-knockout mice demonstrated that the enzyme was important only for absorption of cholesteryl ester (11, 12), which is a minor component of dietary cholesterol and is present at very low levels in bile. Interestingly, CEL is also found in liver where it has been shown to affect HDL metabolism (13). Thus, it may ultimately play an important role in cholesterol metabolism and may yet prove to be a useful drug target for CVD treatment (Camarota and Howies, unpublished). 

Figure 19.3 Lipoprotein metabolism in the human being. Details of HDL metabolism have been omitted. LPL, lipoprotein lipase FFA, free fatty acids CM, chylomicrons A-E, apoproteins A-E HDL, LDL, IDL, and VLDL are high-density, low-density, intermediate-density, and very low density lipoproteins. (Reproduced by permission from Staff writers. Heart-liver transplantation in a child with homozygous familial hypercholesterolemia. Nutr Rev 43 274-278, 1985.)...

Figure 6-11. HDL metabolism. LCAT = lecithin cholesterol acyltransferase.

M. Jaye, K.J. Lynch, J. Krawiec, D. Marchadier, C. Maugeais, K. Doan, V. South, D. Amin, M. Perrone, and D.J. Rader, A novel endothelial-derived lipase that modulates HDL metabolism, Nat. Genet., 1999, 21, 424-428. 

Lamarche B, Rashid S, Lewis GF, etal. HDL metabolism in hypertriglyceridaemic states an overview. Clin Chem Acta.l999 286 145-161. 

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